Artikel
Elevated immunosenescence parameters of CD8+ T cells in CMV-seropositive
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Veröffentlicht: | 1. September 2015 |
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Gliederung
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Introduction: Latent Cytomegalovirus (CMV) infection drives immunosenescence in elderly showing increased CD28- T cells, enhanced peripheral T cell proliferation, TCR repertoire restriction and aberrant IFNγ responses. Reactivations of CMV and abnormal responses towards CMV have been reported in rheumatoid arthritis (RA) in juvenile idiopathic arthritis (JIA).
Methods: To evaluate the associations between latent CMV infection and immunosenescence parameters in autoimmune arthritis, unspecific and CMVpp65-specific IFNgamma responses were analyzed in peripheral CD8+ T cells in 57 RA or 60 JIA patients compared to healthy, age-matched controls by ELISPOT and flow cytometry.
Results: Higher prevalence and concentrations of IgG-anti-CMV were found in RA. RA and JIA patients showed lower unspecific IFNgamma production, lower CD69-mediated activation and lower Ki67+ CD8+ T cell proliferation, but higher intracellular IFNgamma production and increased proportions of CD28-negative T cells after specific CMVpp65 stimulation. CMVpp65-specific cellular reactivity was not altered by blockade of IL-6 or TNFalpha in vitro. JIA patients showed a skewed TCR repertoire towards oligoclonality and less polyclonality.
Conclusion: Our results suggest an efficient control of latent CMV infection by CMVpp65-specific IFNgamma production with expansion of CD28- CD8+ T cells, although lower unspecific intracellular IFNgamma production and peripheral CD8+ T cell activation, as well as proliferation and TCR diversity restriction were found in CMV-seropositive patients with autoimmune arthritis. In vitro blockade of TNFalpha or IL-6 seems not to influence CMVpp65-specific cellular reactivity, but may be studied in the long-term with translation to therapeutic effects of biologics on the need for life-long immunological control of CMV and inflammation.